Hiyama reagent

A valuable feature of the Nin/Crn-mediated Nozaki-Takai-Hiyama-Kishi coupling of vinyl iodides and aldehydes is that the stereochemistry of the vinyl iodide partner is reflected in the allylic alcohol coupling product, at least when disubstituted or trans tri-substituted vinyl iodides are employed.68 It is, therefore, imperative that the trans vinyl iodide stereochemistry in 159 be rigorously defined. Of the various ways in which this objective could be achieved, a regioselective syn addition of the Zr-H bond of Schwartz s reagent (Cp2ZrHCl) to the alkyne function in 165, followed by exposure of the resulting vinylzirconium species to iodine, seemed to constitute a distinctly direct solution to this important problem. Alkyne 165 could conceivably be derived in short order from compound 166, the projected product of an asymmetric crotylboration of achiral aldehyde 168. 

One of the most gentle methods for the generation of reactive allylmetallic reagents was introduced in 1977 by Hiyama and Nozaki1,2,3,33. By the action of two equivalents of chromi-um(II) chloride on allylic halides in tetrahydrofuran at 0°C in the presence of a carbonyl compound, reductive coupling with the formation of a homoallylic alcohol takes place. 

In a recent synthesis of (-i-)-discodermolide, Nozaki-Hiyama reaction of the aldehyde 1617 with the unsaturated Peterson reagent 1618 then treatment with KH in THE gave the diene 1619 in 74% yield [19] (Scheme 10.8). 

Nozaki-Hiyama-Kishi (NHK) reactions215,216 are well known and often employed as a useful method for the synthesis of natural products by coupling of allyl, alkenyl, alkynyl, and aryl halides or triflates with aldehydes. The organochromium reagents are prepared from the corresponding halides or triflates and chromium(ll) chloride, and are employed in polar aprotic solvents (THF, DMF, DMSO, etc.). Subsequently, it was found that nickel salts exhibited a significant catalytic effect on the formation of the C-Cr bond217,218 (Equation (19)). 

The Hiyama coupling offers a practical alternative when selectivity and/or availability of other reagents are problematic. Hiyama et al. coupled alkyltrifluorosilane 74 with 2-bromofuran 73 to give the corresponding cross-coupled product 75 in moderate yield in the presence of catalytic Pd(Ph3P)4 and 3 equivalents of TBAF [65]. In this case, more than one equivalent of fluoride ion was needed to form a pentacoordinated silicate. On the other hand, alkyltrifluorosilane 74 was prepared by hydrosilylation of the corresponding terminal olefin with trichlorosilane followed by fluorination with C11F2. This method provides a facile protocol for the synthesis of alkyl-substituted aromatic compounds. 

Reactions with Organosilicon Reagents The Hiyama Reaction... 

Reaction with Organosilicon Reagents (Hiyama Coupling) 668... 

Likewise, 1,1-dichloroallyllithium preferably reacts C-l with electrophiles63) as is seen from the results of Hiyama et al, who used this reagent for cyclopentenone annulation 64) (Eq. (59)). 

---